Iron deficiency in chronic kidney disease patients with diabetes mellitus

Backgrounds

Iron deficiency has been studied extensively in patients with chronic kidney disease on hemodialysis therapy. However, few studies looked at iron treatment in the non-dialysis chronic kidney disease population.

Acute kidney injury in patients with chronic liver disease

Acute kidney injury(AKI) is a frequent clinical event in patients with liver disease, compounding their prognosis. Furthermore, it is likely that the occurrence of AKI has a detrimental impact on the subsequent renal function and the long-term survival of these patients. Recently, some authors advocated the use of new diagnostic criteria for detecting acute kidney injury in patients with cirrhosis. These criteria are based on the rapidity and extent of the creatinine increase comparing to the basal creatinine and also on the kinetics of diuresis decrease. Although their validity in this population requires further studies to be clearly established, these new criteria could have two advantages:(1) to allow earlier diagnosis of AKI and, thus, hepatorenal syndromefor which earlier intervention could improve patients' survival; and(2) to promote more intensive monitoring of renal function in these patients with high risk of AKI. Finally, recent practice guidelines about the prevention and treatment of general AKI have been published which should be useful in optimising the management of AKI in cirrhotic patients.     

Survival benefit of nephrologic care in patients with diabetes mellitus and chronic kidney disease

BACKGROUND: The association of nephrologic care and survival in patients with diabetes mellitus and chronic kidney disease is unknown. METHODS: Using data from 1997 to 2000, we conducted a retrospective cohort study of Veterans Health Administration clinic users having diabetes mellitus and stage 3 or 4 chronic kidney disease. The baseline period was 12 months and median follow-up was 19.3 months. Degree of consistency of visits to a nephrologist, defined as the number of calendar quarters in which there was 1 visit or more (range, 0-4 quarters), and covariates were calculated from the baseline period. The outcome measure was dialysis-free death. RESULTS: Of 39,031 patients, 70.0%, 22.4%, and 7.6% had early stage 3, late stage 3, and stage 4 chronic kidney disease, respectively, and 3.1%, 9.5%, and 28.2%, respectively, visited a nephrologist. Dialysis-free mortality rates were 9.6, 14.1, and 19.4, respectively, per 100 person-years. More calendar quarters with visits to a nephrologist were associated with lower mortality: adjusted hazard ratios were 0.80 (95% confidence interval, 0.67-0.97), 0.68 (95% confidence interval, 0.55-0.86), and 0.45 (95% confidence interval, 0.32-0.63), respectively, when the groups having 2, 3, and 4 visits were compared with those who had no visits. One visit only was not associated with a difference in mortality when compared with no visits (adjusted hazard ratio,1.02; 95% confidence interval, 0.89-1.16). CONCLUSIONS: The consistency of outpatient nephrologic care was independently associated in a graded fashion with lower risk of deaths in patients with diabetes and moderately severe to severe chronic kidney disease. However, only a minority of patients had any visits to a nephrologist.     

Acute kidney injury and chronic kidney disease after liver transplant: A retrospective observational study

Background and rationaleChronic kidney disease remains an important risk factor for morbidity and mortality among LT recipients, but its exact incidence and risk factors are still unclear.Material and methodsWe carried out a retrospective cohort study of consecutive adults who underwent liver transplant (January 2009–December 2018) and were followed (at least 6 months) at our institution. CKD was defined following the Kidney Disease: Improving Global Outcomes (KDIGO) 2012 Clinical Practice Guidelines. Long-term kidney function was classified into 4 groups: no CKD (eGFR, ≥60 mL/min/1.73 m²), mild CKD (eGFR, 30–59 mL/min/1.73 m²), severe CKD (eGFR, 15–29 mL/min/1.73 m²), and end-stage renal disease (ESRD).ResultsWe enrolled 410 patients followed for 53.2 ± 32.6 months. 39 had CKD at baseline, and 95 developed de novo CKD over the observation period. There were 184 (44.9%) anti-HCV positive, 47 (11.5%) HBsAg positive, and 33 (8.1%) HBV/HDV positive recipients. Recipient risk factors for baseline CKD were advanced age (P = 0.044), raised levels of serum uric acid (P < 0.0001), and insulin dependent DM (P = 0.0034). Early post-transplant AKI was common (n = 95); logistic regression analysis found that baseline serum creatinine was an independent predictor of early post-LT AKI (P = 0.0154). According to our Cox proportional hazards model, recipient risk factors for de novo CKD included aging (P < 0.0001), early post-transplant AKI (P = 0.007), and baseline serum creatinine (P = 0.0002). At the end of follow-up, there were 116 LT recipients with CKD – 109 (93.9%) and 7 (6.1%) had stage 3 and advanced CKD, respectively. Only two of them are undergoing long-term dialysis.ConclusionThe incidence of CKD was high in our cohort of LT recipients, but only a slight decline in kidney function over time was recorded. Prevention of post-transplant AKI will improve kidney function in the long run. We need more studies to analyze the function of kidneys among LT recipients over extended follow-ups and their impact on mortality.     

Prevalence of chronic kidney disease in Brazilians with arterial hypertension and/or diabetes mellitus

The present study aimed to evaluate the prevalence of chronic kidney disease (CKD) in individuals with arterial hypertension (AH) and/or diabetes mellitus (DM) accompanied by Primary Health Care (PHC) in Brazil. The estimated glomerular filtration rate (eGFR) based on creatinine, and urinary albumin‐to‐creatinine ratio (ACR) were measured in 841 subjects with AH and/or DM, followed by PHC in the city of Viçosa. The CKD was diagnosed according to KDIGO criteria. Sociodemographic, clinical, and anthropometric factors related to the prevalence of CKD were investigated through multiple logistic regression. The prevalence of hidden CKD was 15.4%. Of these, 7.5% were identified by albuminuria (ACR ≥30 mg/g) with slightly decreased eGFR. Age, baseline disease, waist circumference (WC), and systolic blood pressure remained associated with CKD after multivariate analysis. The two major risk factors for hidden CKD were the presence of AH in association with DM and an increase in age. Hidden CKD was more common within people with AH and DM, and with high WC, glycosylated hemoglobin, and serum phosphorus as well as male gender and decreased serum albumin. This knowledge of risk associations can help avoid progression to CKD.     

Effect of diabetes mellitus on markers of left ventricular dysfunction in chronic kidney disease

ObjectivesTo identify markers of left ventricular dysfunction in chronic kidney disease (CKD) and the effects of diabetes mellitus on them.MethodsThis was a cross sectional study of 200 consecutive chronic kidney disease patients (stage III-V). Echocardiographic assessment of left ventricular function including left ventricular ejection fraction (LVEF), left ventricular mass index (LVMI), left atrial volume, grade of diastolic dysfunction, E/E’, left and right ventricular myocardial performance indices (LVMPI, RVMPI) were compared between diabetic and non-diabetic CKD.ResultsLVMI significantly increased with increasing stage of CKD (p < 0.001) in both diabetics (158.82 ± 48.76 gm/m² in stage III to 201.06 ± 63.62 gm/m² in stage V) and non-diabetics (133.14 ± 43.06 gm/m² stage III to 196.24 ± 58.75 gm/m² in stage V). This was significantly higher among diabetics of similar CKD stage compared to non-diabetics (p = 0.001). The LVEF worsened with increasing stage of CKD (p = 0.002) and was significantly reduced in diabetic patients (LVEF 61.96 ± 8.48 % in stage III CKD to 51.62 ± 13.45 % in stage V CKD) (p < 0.001). Diastolic dysfunction (Grades ≥2) and LA volume increased significantly with stage of CKD (p < 0.001) and was higher among diabetics (p = 0.048). Pulmonary artery systolic pressure (PASP) increased with increasing stage of CKD (p < 0.001), and was higher among diabetics (p = 0.035). E/E’ worsened significantly with increasing stage of CKD and was also significantly higher in diabetics (p < 0.001). LVMPI (p < 0.001) and RVMPI (p < 0.001) were significantly reduced with worsening stage of CKD and in diabetics.ConclusionAdvancing CKD stage was linearly associated with progressive left ventricular dysfunction which was significantly greater in diabetics.     

Pathophysiology, prevention and management of chronic kidney disease in the hypertensive patient with diabetes mellitus

The authors concisely review the main clinical issues arising in the management of the hypertensive patient with type 2 diabetes, in whom chronic kidney disease is prevalent and heralds increased cardiovascular morbidity and mortality. Special attention is paid to the clinical meaning, relevance and limits of albumin excretion and glomerular filtration rate, the two widely used markers of reduced kidney function during the course of chronic diseases like diabetes and hypertension. The main therapeutic strategies involving blood pressure and glycemic control, treatment of dyslipidemia and improvement of lifestyle are discussed from the viewpoint of a general practitioner dealing with the clinical complexity of these patients.     

芪药消渴胶囊逆转2型糖尿病慢性肾脏疾病白蛋白尿的临床观察

目的 观察芪药消渴胶囊对糖尿病慢性肾脏疾病（CKD）白蛋白尿的影响. 方法 采用多中心、随机、双盲、安慰剂对照试验,共224例UAlb/Cr 30～299 mg/24 h患者纳入研究,其中试验（Tre）组116例,对照（PC）组108例,两组在接受常规治疗的基础上,Tre组加用芪药消渴胶囊,PC组加用安慰剂,治疗16周.比较两组治疗前后UAlb/Cr、肾功能、血糖、血脂等指标的变化. 结果 与治疗前相比,治疗后两组UAlb/Cr、肾功能、血糖、血脂等指标均有所改善（P＜0.05）,Tre组与PC组相比差异有统计学意义（P＜0.05）. 结论 芪药消渴胶囊能够逆转患者UAlb/Cr 30～299 mg/24 h水平,保护肾功能,延缓CKD的进展.     

Cardiovascular disease risk in youth with diabetes mellitus

In the United States, cardiovascular disease is the leading cause of mortality in adults with diabetes over age 30 years. Studies in persons without diabetes have shown that atherosclerosis, a central factor in cardiovascular disease, begins in childhood and the presence of cardiovascular disease risk factors in youth lead to increased cardiovascular disease risk in adults. Therefore, youth with diabetes are at increased risk for developing cardiovascular disease as adults and there is a role for risk factor screening and addressing modifiable factors to lower cardiovascular disease risk starting in childhood. This paper reviews the literature on traditional cardiovascular disease risk factors in youth with diabetes including hyperglycemia, hypertension, dyslipidemia, smoking, obesity and family history of cardiovascular disease with an emphasis on type 1 diabetes as well as current American Diabetes Association guidelines for screening and treatment of modifiable risk factors. Current roles of inflammatory markers and measures of subclinical vascular changes such as arterial stiffness are also discussed.     

Clinicopathological features in 507 patients with type 2 diabetes mellitus complicated with chronic kidney disease

正Objective To analyze the clinicopathological features in diabetic kidney disease (DKD) and non-diabetic kidney disease (NDKD) patients,and provide reference for patients who will receive renal biopsy with diabetes mellitus complicated with chronic kidney disease.Methods The patients with type 2 diabetes mellitus complicated with chronic kidney disease who underwent renal bi-     

Acute kidney injury in acute on chronic liver failure

Acute on chronic liver failure (ACLF) is a distinct clinical entity; however, there is still debate in the way it is defined in the East as compared to the West, especially with respect to incorporation of kidney dysfunction or failure in the definition of ACLF. Kidney dysfunction is defined as serum creatinine between 1.5 and 1.9 mg/dl and kidney failure as serum creatinine of more than 2 mg/dl or requirement of renal replacement therapy according to the EASL-CLIF Consortium. Kidney dysfunction or failure is universally present in patients with ACLF according to the definition by the EASL-CLIF Consortium while on the contrary the APASL definition of ACLF does not incorporate kidney dysfunction or failure in its definition. Recently, both the diagnosis and management of renal failure in patients with cirrhosis has changed with the advent of the acute kidney injury (AKI) criteria defined as an abrupt decline in renal functions, characterized by an absolute increase in serum creatinine of 0.3 mg/dl within 48 h or an increase of more than 50 % from baseline, which is known or presumed to have occurred in the previous 7 days. Further, recent studies in patients with cirrhosis have shown the utility of biomarkers for the diagnosis of AKI. The present review covers the pathogenetic mechanisms, diagnosis, prognosis as well as management of AKI in patients with ACLF from both a Western as well as an Eastern perspective. The review identifies an unmet need to diagnose AKI and prevent this ominous complication in patients with ACLF.     

Obesity,diabetes, and chronic kidney disease

Similar to diabetes, obesity is associated with the early onset of glomerulomegaly, hemodynamic changes of a hyperfiltering kidney, and increased albuminuria, which are potentially reversible with weight loss. However, the pathologic lesions of focal segmental glomerulosclerosis in experimental models of sustained obesity, and in obese humans presenting with massive proteinuria, are different from those of classic diabetic nephropathy. In addition, several observational, cross-sectional, and longitudinal studies document obesity as an independent risk factor for the onset, aggravated course, and poor outcomes of chronic kidney disease, even after adjustment for confounding comorbidities, including diabetes and hypertension, the two major causes of chronic kidney disease.     

Incremental risk of cardiovascular disease and/or chronic kidney disease for future ASCVD and mortality in patients with type 2 diabetes mellitus: ACCORD trial

BackgroundCardiovascular disease (CVD) and chronic kidney disease (CKD) are complications of type 2 diabetes mellitus (DM). Current cholesterol guidelines recommend the same prevention strategy for patients with DM alone as patients with DM + CKD. However, the incremental risk of these common complications for incident cardiovascular disease and mortality has not been well studied.MethodsWe compared the incremental risk of having DM + CKD, DM + CVD and DM + CVD + CKD in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial participants for incident CVD as the primary outcome and all-cause mortality.ResultsAfter a mean (SD) follow up of 4.7(1.4) years, 1,046(10%) participants developed CVD. DM +vCKD, DM + CVD, and DM + CKD + CVD had a significantly increased risk of the primary outcome compared to DM alone [adjusted hazard ratio(95%CI): 1.41 (1.06-1.89), p = 0.02; 2.20 (1.92-2.53), p < 0.001); 2.35 (1.81-3.04), p < 0.001), respectively]. All-cause mortality had a graded increased risk compared to the reference group [adjusted hazard ratio(95%CI): 1.39 (1.01-1.90), p = 0.04; 1.29 (1.51-2.12), p < 0.0001; 2.36 (1.75-3.13), p < 0.0001), respectively].ConclusionOur post hoc analysis shows an incremental graded risk for CVD outcomes and all-cause mortality with the development of CKD and/or CVD in individuals with DM.     

Insulin like growth factor 1 is linked to higher cardiovascular risk score in adults with type 2 diabetes mellitus and chronic kidney disease

IntroductionInsulin-like growth factor-1 (IGF-1) is a peptide that shares sequence homology with insulin and has endocrine, paracrine and autocrine functions, acts on endothelial cells, and stimulates angiogenesis. IGF1 also affects renal hemodynamics both directly and indirectly by interacting with the renin-angiotensin system.ObjectiveThe study aimed at detecting a relation between age-adjusted IGF1 (AAIGF1) and cardiovascular risk score in adults with type 2 diabetes mellitus and chronic kidney disease.DesignPatients were 90 females and 42 males with different stages of CKD ranging from 0 to 4. After taking a consent, serum IGF1 was recorded and adjusted for the age of the patient using the IGF1 score equation: {[(log IGF-1 + 0.00625xage)-2.555]/0.104}.Both univariate and multivariate regression analyses of AAIGF1 to different metabolic parameters and microvascular complications of type 2 DM were done. A ROC curve for CV risk score was issued.ResultsAAIGF1 showed a significant bidirectional change with the stage of CKD. Univariate analysis was done including cardiovascular parameters in relations to AAIGF1. A significant positive correlation was found between AAIGF1 and CV risk score (B = 0.036, p = 0.003), SBP (B = 0.030, P = 0.004) and DBP (B = 0.071, P = 0.000), with a reciprocal relation to EF (B = -0.050, P = 0.016). Multivariate regression showed a significant correlation between AAIGF1 and age, HOMAIR, HOMAB, Uric acid. A ROC curve with AUC of 0.675, P = 0.003, showed that AAIGF1 of approximately −1.7 is a cut off for intermediate CV risk (10 year risk score >7.5%).ConclusionAAIGF1 shows a bidirectional relation to the grade of chronic kidney disease in adults with type 2 DM. A cut off point for AAIGF1 was set to indicate intermediate CV risk score, which can encourage using AAIGF1 as a prognostic marker for higher CV risk score. Medications that modulate IGF1 level can affect CV risk.     

Evidence for two distinct phenotypes of chronic kidney disease in individuals with type 1 diabetes mellitus

Aims/hypothesis

In a retrospective, observational, cross-sectional, single-centre study, we assessed the prevalence and correlates of different CKD phenotypes (with and without albuminuria) in a large cohort of patients of white ethnicity with type 1 diabetes.

Methods

From 2001 to 2009, 408 men and 369 women with type 1 diabetes (age 40.2 ± 11.7 years, diabetes duration 19.4 ± 12.2 years, HbA_1c 7.83 ± 1.17% [62.0 ± 12.9 mmol/mol]) were recruited consecutively. Albumin-to-creatinine ratio (ACR) and eGFR (Modification of Diet in Renal Disease) were obtained for all individuals, together with CKD stage. Diabetic retinopathy and peripheral polyneuropathy were detected in 41.5% and 8.1%, respectively, and cardiovascular disease (CVD) occurred in 8.5%. Adjudications of CKD phenotype were made by blinded investigators.

Results

Normo- (ACR <3.4), micro- (ACR 3.4–34) or macroalbuminuria (ACR ≥34 mg/mmol) were present in 91.6%, 6.4% and 1.9% of individuals, respectively. eGFR categories 1 (≥90 ml min^?1 [1.73 m]^?2), 2 (60–89 ml min^?1 [1.73 m]^?2) and 3 (<60 ml min^?1 [1.73 m]^?2) were present in 57.3%, 39.0% and 3.7%, respectively. The majority of participants had no CKD (89.4%), while stages 1–2 and ≥3 CKD were detected in 6.8% and 3.7%, respectively. The albuminuric (Alb⁺) and non-albuminuric (Alb^?) phenotypes were present in 12 (41.4%) and 17 (58.6%) individuals with stage ≥3 CKD, respectively. Individuals with an ACR <3.4 mg/mmol were subdivided into those with normal albuminuria (<1.1 mg/mmol; 77.2%) and mildly increased albuminuria (1.1–3.4 mg/mmol; 14.4%), and individuals with stage 2 CKD were subdivided into those with eGFR 75–89 ml min^?1 [1.73 m]^?2 and 60–74 ml min^?1 [1.73 m]^?2. ACR <3.4 mg/mmol (88.7%) and even <1.1 mg/mmol (70.4%) were common in individuals with eGFR 60–74 ml min^?1 [1.73 m]^?2. The prevalence of ACR <1.1 mg/mmol was lower but still significant (34.5%) in those with stage ≥3 CKD. In logistic regression analysis, stages 1–2 and ≥3 CKD were independently associated with age, HbA_1c, γ-glutamyltransferase, fibrinogen, hypertension, but not with sex, BMI, smoking, HDL-cholesterol or triacylglycerol. Inclusion of advanced retinopathy removed HbA_1c from the model. The CKD Alb⁺ phenotype correlated with diabetes duration, HbA_1c, HDL-cholesterol, fibrinogen and hypertension, while the CKD Alb^? phenotype was associated with age and hypertension, but not with diabetes duration, HbA_1c and fibrinogen.

Conclusions/interpretation

The Alb^? CKD phenotype is present in a significant proportion of individuals with type 1 diabetes supporting the hypothesis of two distinct pathways (Alb⁺ and Alb^?) of progression towards advanced kidney disease in type 1 diabetes. These are probably distinct pathways as suggested by different sets of covariates associated with the two CKD phenotypes.